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子宫内膜异位症和子宫内膜异位症微环境的体外建模——挑战与最新进展。

In vitro modeling of endometriosis and endometriotic microenvironment - Challenges and recent advances.

机构信息

Department of Biotechnology and Food Microbiology, Poznan University of Life Sciences, 48 Wojska Polskiego St., 60-627 Poznan, Poland.

Department of Biotechnology and Food Microbiology, Poznan University of Life Sciences, 48 Wojska Polskiego St., 60-627 Poznan, Poland.

出版信息

Cell Signal. 2022 Sep;97:110375. doi: 10.1016/j.cellsig.2022.110375. Epub 2022 Jun 9.

DOI:10.1016/j.cellsig.2022.110375
PMID:35690293
Abstract

Endometriosis is a chronic condition with high prevalence in reproductive age women, defined as the growth of endometrial tissue outside the uterine cavity, most commonly on the pelvic peritoneum. The ectopic endometrial lesions exist in a unique microenvironment created by the interaction of epithelial, stromal, endothelial, glandular, and immune cell components, dominated by inflammatory, angiogenic, and endocrine signals. Current research is directed at understanding the complex microenvironment of the lesions and its relationship with different endometriosis stages, phenotypes, and disease symptoms and at the development of novel diagnostic and therapeutic concepts that minimalize the undesirable side effects of current medical management. Recreating pathophysiological cellular and molecular mechanisms and identifying clinically relevant metrics to assess drug efficacy is a great challenge for the experimental disease models. This review summarizes the complete range of available in vitro experimental systems used in endometriotic studies, which reflect the multifactorial nature of the endometriotic lesion. The article discusses the simplistic in vitro models such as primary endometrial cells and endometriotic cell lines to heterogeneous 2D co-cultures, and recently more common, 3D systems based on self-organization and controlled assembly, both in microfluidic or bioprinting methodologies. Basic research models allow studying fundamental pathological mechanisms by which menstrual endometrium adheres, invades, and establishes lesions in ectopic sites. The advanced endometriosis experimental models address the critical challenges and unsolved problems and provide an approach to drug screening and medicine discovery by mimicking the complicated behaviors of the endometriotic lesion.

摘要

子宫内膜异位症是一种在育龄妇女中高发的慢性疾病,定义为子宫内膜组织在子宫腔外生长,最常见于盆腔腹膜。异位的子宫内膜病变存在于由上皮、基质、内皮、腺体和免疫细胞成分相互作用形成的独特微环境中,以炎症、血管生成和内分泌信号为主导。目前的研究旨在了解病变的复杂微环境及其与不同子宫内膜异位症阶段、表型和疾病症状的关系,并开发新的诊断和治疗概念,以最大限度地减少当前医学管理的不良副作用。重现病理生理细胞和分子机制,并确定临床相关的指标来评估药物疗效,这对于实验性疾病模型来说是一个巨大的挑战。这篇综述总结了子宫内膜异位症研究中使用的各种体外实验系统,这些系统反映了子宫内膜异位症病变的多因素性质。文章讨论了简单的体外模型,如原代子宫内膜细胞和子宫内膜异位症细胞系,以及最近更常见的基于自组织和受控组装的异质 2D 共培养物,以及基于微流控或生物打印方法的 3D 系统。基础研究模型允许研究月经子宫内膜在异位部位黏附、侵袭和建立病变的基本病理机制。先进的子宫内膜异位症实验模型解决了关键的挑战和未解决的问题,并通过模拟子宫内膜异位症病变的复杂行为,为药物筛选和药物发现提供了一种方法。

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